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Prostate cancer (PCa) patients with mismatch repair (MMR) genes mutations are potentially responsive to immune checkpoint blockade (ICB). However, aberrations in MMR genes were rare in PCa and there is evidence that MMR genes mutations are highly ethnic specific. Thus, the prevalence and clinical characteristics of this subgroup in Chinese PCa patients are largely unknown. Furthermore, why some of these patients do not respond to ICB also remains unclear. Here, we analyzed the sequencing data from 3338 Chinese PCa patients to profile the mutation spectrum of the MMR genes. We found that in metastatic disease, the pathogenic mutation frequency of MMR genes in Chinese PCa patients was higher than that in the Caucasus population (4.8 vs 2.2%, P = 0.006) and the mutation carriers responded poorer to androgen deprive therapy (ADT) and abiraterone than non-carriers. Besides, we reported a multi-institutional cases series of 11 PCa patients with mismatch repair deficiency (dMMR) or microsatellite instability high (MSI-H) who received programmed cell death receptor-1 (PD-1) inhibitors, and performed multiplex immunohistochemistry (mIF) to explore the relationship between tumor immune microenvironment (TIME) and response to ICB. The results showed that the responders had higher density of intratumoral CD8+ T cells than non-responders. Our data suggested MMR genes mutations may be more common in Chinese PCa patients, and it is associated with poorer response to hormonal therapies. We propose that the density of intratumoral CD8+ T cells could be a promising predictor to help further subdivide the population of PCa patients who can benefit from immunotherapy. [ABSTRACT FROM AUTHOR]

Objectives: To develop and validate a predictive model based on clinical features and multiparametric magnetic resonance imaging (mpMRI) to reduce unnecessary systematic biopsies (SBs) in biopsy-naïve patients with suspected prostate cancer (PCa). Methods: A total of 274 patients who underwent combined cognitive MRI-targeted biopsy (MRTB) with SB were retrospectively enrolled and temporally split into development (n = 201) and validation (n = 73) cohorts. Multivariable logistic regression analyses were used to determine independent predictors of clinically significant PCa (csPCa) on cognitive MRTB, and the clinical, MRI, and combined models were established respectively. Area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analyses were assessed. Results: Prostate imaging data and reporting system (PI-RADS) score, index lesion (IL) on the peripheral zone, age, and prostate-specific antigen density (PSAD) were independent predictors and included in the combined model. The combined model achieved the best discrimination (AUC 0.88) as compared to both the MRI model incorporated by PI-RADS score, IL level, and zone (AUC 0.86) and the clinical model incorporated by age and PSAD (AUC 0.70). The combined model also showed good calibration and enabled great net benefit. Applying the combined model as a reference for performing MRTB alone with a cutoff of 60% would reduce 43.8% of additional SB, while missing 2.9% csPCa. Conclusions: The combined model based on clinical and mpMRI findings improved csPCa prediction and might be useful in making a decision about which patient could safely avoid unnecessary SB in addition to MRTB in biopsy-naïve patients. Critical relevance statement: The combined model based on clinical and mpMRI findings improved csPCa prediction and might be useful in making a decision about which patient could safely avoid unnecessary SB in addition to MRTB in biopsy-naïve patients. Key points: • Age, PSAD, PI-RADS score, and peripheral index lesion were independent predictors of csPCa. • Risk models were used to predict the probability of detecting csPCa on cognitive MRTB. • The combined model might reduce 43.8% of unnecessary SBs, while missing 2.9% csPCa. [ABSTRACT FROM AUTHOR]

Thus, we aimed to develop the APGRC (Asian PCa Germline Risk Calculator), a risk assessment nomogram for predicting the probability of carrying germline PVs in 14 PCa predisposition DDR genes. Dear Editor, Prostate cancer (PCa) is a prominent global cancer among men, estimated at 1.3 million diagnoses and 359 thousand deaths in 2018,[1] with a strong hereditary component. [Extracted from the article]

CDK12 (Cyclin-Dependent Kinase 12)-mutated prostate cancer patients often respond badly to current therapies. Immunotherapy and platinum-based chemotherapy are recommended based on the molecular features of CDK12-mutated tumors, but the reported patient outcomes are still unsatisfying. Here we report a prostate cancer patient with CDK12 somatic mutation who received multiple therapy options, including platinum-based chemotherapy and immunotherapy. His sequential circulating tumor DNA (ctDNA) -based liquid biopsy tests showed that his original CDK12 mutation fell undetectable twice. This phenomenon was observed only when he was responding well to platinum-based chemotherapy. His responses to immunotherapy were not satisfying. This case indicates that platinum-based chemotherapy can be a good option for treating patients with CDK12 mutation. More importantly, dynamic ctDNA-based liquid biopsies to monitor patients' CDK12 mutation status are critical in evaluating patients' response and tolerance during platinum-based chemotherapy, therefore may lead to a better overall prognosis. In conclusion, CDK12-mutated prostate cancer patients are likely to benefit from platinum-based chemotherapy, especially with the help of dynamic ctDNA-based liquid biopsies to monitor their CDK12 mutation status. [ABSTRACT FROM AUTHOR]

Background: To use ddPCR to quantify plasma exosomal class III β‐tubulin (βIII‐tubulin, TUBB3, encoded by the TUBB3 gene) mRNA expression in metastatic castration‐resistant prostate cancer (mCRPC) patients, and study the association of this expression with abiraterone efficacy. Methods: Blood samples were prospectively collected from 52 mCRPC patients using abiraterone as first‐line therapy to measure plasma exosomal TUBB3 mRNA expression value before the initiation of abiraterone. Study endpoints were PSA response rate, PSA‐progression‐free survival (PSA‐PFS), and overall survival (OS, from CRPC to death). Results: Patients with positive exosomal TUBB3 expression showed shorter PSA‐PFS (negative TUBB3 vs. positive TUBB3: 11.0 vs. 7.9 months; p = 0.014). Further analysis demonstrated that patients with strongly positive exosomal TUBB3 (>20 copies/20 µl) was associated with even shorter PSA‐PFS (negative TUBB3 vs. positive TUBB3 [<20 copies/20 µl] vs. strongly positive TUBB3 [>20 copies/20 µl]: 11.0 vs. 8.3 vs. 3.6 months, p = 0.005). In multivariate analyzes, TUBB3 (+) (HR: 2.114, p = 0.033) and ECOG score >2 (HR: 3.039, p = 0.006) were independent prognosticators of poor PSA‐PFS. PSA response and OS did not present significant differences. Conclusion: The exosomal TUBB3 mRNA expression level is associated with poor PSA‐PFS of abiraterone in mCRPC patients. The detection of exosomal TUBB3 can be valuable in their management. [ABSTRACT FROM AUTHOR]

Background: To assess the efficacies and potential predictors of a corticosteroid switch in metastatic castration-resistant prostate cancer (mCRPC) patients with biochemical progression on abiraterone acetate plus prednisone (A + P).Methods: Patients with mCRPC treated between April 2016 and August 2020, who experienced biochemical progression on A + P and then switched to A plus dexamethasone (D), were retrospectively identified. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were PSA response, overall survival (OS), and safety.Results: One hundred and thirty consecutive cases were enrolled. The median PFS and OS on A + D were 5.0 and 18.7 months, respectively. The best PSA decline of ≥50% (PSA50) and ≥ 30% (PSA30) were observed in 29.2 and 46.2% patients, respectively. Lower PSA at corticosteroid switch (≤ 20 ng/mL; median PFS, HR 0.63, p = 0.019; median OS, HR 0.38, p = 0.001) and longer mCRPC-free survival (≥ 18 months; median PFS, HR 0.61, p = 0.013; median OS, HR 0.51, p = 0.015) were identified as independent prognostic predictors associated with longer PFS and OS. A risk stratification tool was developed to select candidates for corticosteroid switch based on the independent prognostic predictors of PFS and OS.Conclusions: A corticosteroid switch from prednisone to dexamethasone is effective for mCRPC which progressed on A + P treatment. Patients with lower PSA at corticosteroid switch and/or longer mCRPC-free survival may gain more benefits by the corticosteroid switch. [ABSTRACT FROM AUTHOR]

Pelvic lymph node dissection (PLND) represents the gold standard for nodal staging in PCa and is recommended for patients with a probability of lymph node invasion (LNI) >5%. However, the therapeutic role of PLND and its extent remains a debate. In this study, data of 20,668 patients treated with radical prostatectomy (RP) with and without PLND from SEER database between 2010 and 2015 were retrospectively analyzed. All patients had a risk of LNI >5% according to 2012-Briganti nomogram. Propensity score matching (PSM) was performed to balance baseline characteristics between patients with and without PLND. Kaplan-Meier curves and Cox regression were used to evaluate the impacts of the PLND and its extent on cancer-specific survival (CSS) and overall survival (OS). In overall cohort, patients with PLND were associated with more aggressive clinicopathologic characteristics and had poorer survival compared to those without PLND (5-year CSS rate: 98.4% vs. 99.7%, p < 0.001; 5-year OS rate: 96.3% vs. 97.8%, p < 0.001). In the post-PSM cohort, no significant difference in survival was found between patients with and without PLND (5-year CSS rate: 99.4% vs. 99.7%, p = 0.479; 5-year OS rate: 97.3% vs. 97.8%, p = 0.204). In addition, the extent of PLND had no impact on prognosis (all p > 0.05). Subgroup analyses reported similar negative findings. In conclusion, neither PLND nor its extent was associated with survival in North American patients with a risk of LNI >5%. The cut-off point of 5% probability of LNI might be too low to show benefits in survival in patients underwent PLND. [ABSTRACT FROM AUTHOR]